The inability to transduce a sufficient fraction of the stem cell pool is a major limitation of gene therapy for sickle cell disease, a painful and debilitating blood disorder that afflicts about one in every 1000 Americans of African descent. In this project we are identifying the optimal conditions for mobilizing hemopoietic stem cells from the bone marrow into the peripheral blood so the greatest number of stem cells can be harvested. We are also investigating optimal conditions for transduction of these cells ex vivo to correct the genetic defect in the sickle cell or in cells from other hemoglobin diseases. We have found that the stem cells from the different species of nonhuman primates vary in their ability to be transduced with our retroviral constructs.